In acute fetal anemia there is redistribution of blood flow toward the brain and heart with no change in blood pressure or cardiac output. Urine flow, glomerular filtration and sodium excretion decrease. In contrast, in chronic fetal anemia we have found generalized vasodilation with an increase in blood flow to all tissues except the placenta. Despite an increase in cardiac output, mean arterial pressure falls. Notably, renal blood flow nearly doubles. In the proposed studies we plan to determine the role of the kidney in the fetal adaptation to chronic anemia. The purpose is to understand the hemodynamic mechanisms of adaptation to chronic fetal anemia and to relate these to the mechanisms which generate extravascular fluid accumulation. Furthermore, we hope these studies will provide insight into disease processes in human fetuses in which chronic anemia is part of the pathophysiology. Specifically, we will test the following hypotheses: (1) In the anemic fetus, the kidneys, by releasing renin, contribute significantly to the maintenance of mean arterial pressure and thereby placental blood flow. We will determine the temporal activation of renin-angiotensin, arginine vasopressin, and catecholamines in response to chronic fetal anemia and evaluate with selective blockade of these systems their individual roles in controlling blood pressure and regional blood flow. (2) The increase in renal blood flow is accompanied by an increase in urine flow, glomerular filtration rate, and sodium excretion. In turn, the increase in urine flow results in polyhydramnios. (3) Renal tubular reabsorption of salt and water in chronic anemia is limited by oxygen availability. If this is the case, relative to controls, the kidneys of anemic fetuses will have reduced oxygen uptake, and decreased ATP levels, and will shift from lactate uptake towards lactate production. (4) In chronic fetal anemia renal osmotic clearance is increased. The fetus that is chronically anemic and nephrectomized will increase plasma osmolality as well as extravascular fluid when compared to anemic fetuses with intact kidneys.